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,C18H15ClN2O2,326.7855,5-(4-chlorophenyl)-8-methyl-6,7,8,9-t

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摘 要:,C18H15ClN2O2,326.7855,5-(4-chlorophenyl)-8-methyl-6,7,8,9-tetrahydro-1H-pyrrolo[3,2-h]isoquinoline-2,3-dione
  • 【化学名】5-(4-chlorophenyl)-8-methyl-6,7,8,9-tetrahydro-1H-pyrrolo[3,2-h]isoquinoline-2,3-dione
  • 【CAS登记号】
  • 【结构式】,C18H15ClN2O2,326.7855,5-(4-chlorophenyl)-8-methyl-6,7,8,9-t--药物合成数据库
  • 【分子式】C18H15ClN2O2
  • 【分子量】326.7855
  • 【来源】
  • 【合成情况】 
  • 〖目标产物〗NS-417
  • 〖合成路线〗
  • 〖合成方法〗Nitration of 5-bromoisoquinoline (I) employing KNO3 in H2SO4 provides 5-bromo-8-nitroisoquinoline (II). Quaternization of isoquinoline (II) with dimethyl sulfate, followed by reduction of the resultant N-methyl isoquinolinium salt (III) with NaBH4 in cold HOAc furnishes the tetrahydroisoquinoline (IV). Subsequent Suzuki coupling between the bromotetrahydroisoquinoline (IV) and 4-chlorophenylboronic acid (V) yields the 5-aryl isoquinoline derivative (VI). The nitro group of (VI) is further reduced to amine (VII) by catalytic hydrogenation over Raney nickel. The key isatin compound (IX) is then obtained by condensation of amine (VII) with chloral (VIII) in the presence of hydroxylamine hydrochloride and sodium sulfate. Finally, isatin (IX) is converted to the desired oxime by treatment with hydroxylamine hydrochloride in EtOH.
  • 〖参考〗Wtjen, F.; Drejer, J. (NeuroSearch A/S); AMPA antagonists and a method of treatment therewith. EP 0698025; JP 1996510221; US 5780493; US 5843945; WO 9426747
  • 〖目标产物〗NS-417
  • 〖合成路线〗
  • 〖合成方法〗Nitration of 5-bromoisoquinoline (I) employing KNO3 in H2SO4 provides 5-bromo-8-nitroisoquinoline (II). Quaternization of isoquinoline (II) with dimethyl sulfate, followed by reduction of the resultant N-methyl isoquinolinium salt (III) with NaBH4 in cold HOAc furnishes the tetrahydroisoquinoline (IV). Subsequent Suzuki coupling between the bromotetrahydroisoquinoline (IV) and 4-chlorophenylboronic acid (V) yields the 5-aryl isoquinoline derivative (VI). The nitro group of (VI) is further reduced to amine (VII) by catalytic hydrogenation over Raney nickel. The key isatin compound (IX) is then obtained by condensation of amine (VII) with chloral (VIII) in the presence of hydroxylamine hydrochloride and sodium sulfate. Finally, isatin (IX) is converted to the desired oxime by treatment with hydroxylamine hydrochloride in EtOH.
  • 〖参考〗Moeller, A.; Peters, D.; Groenborg, M. (NeuroSearch A/S); Isatine derivs. with neurotrophic activity. EP 1255734; US 2003040518; WO 0155110
 
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